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lipoblastoma

Friday 7 October 2005

Definition: Lipoblastoma is a rare benign tumor that arises from embryonic adipose tissue and usually occurs in young children. It is a lobulated, localized (lipoblastoma) or diffuse (lipoblastomatosis) tumor, resembling fetal adipose tissue.

82% of lipoblastomas had rearrangement of the 8q11 approximately q13 region. These rearrangements target the PLAG1 gene, which becomes upregulated through promoter swapping.

Epidemiology

Both types of tumor are most commonly found in the first three years of life. They may occasionally be found at birth or in older children. There is male predilection.

Localization

The extremities are most common location but location in mediastinum, retroperitoneum and head and neck areas was described.

Clinical synopsis

Most patients present with slow growing soft tissue nodule/mass, well circumscribed and confined to the subcutis in case of lipoblastoma , infiltrating deeper muscle in case of lipoblastomatosis.

- Benign
- Infants and young children (<5 years) almost exclusively1–5
- Commonly proximal lower and upper extremities
- sex ratio M/F = 1.7 (#19738456#)
- Age at diagnosis ranges from 3 months to 16 years with 22% in the first year, 68% at 1 to 9 years, and 10% at 10 to 16 years. (#19738456#)
- Localization:

  • trunk (64%)
  • extremities (27%)
  • head/neck (8%). Forty-six percent had
    - one or more recurrences (46%)
    - tumor diameter ranges from 1.2 to 15.5 cm
    - white to yellow cut surface
    - variable lobulation and myxoid change.

Macroscopy

- Benign, lobulated (lipoblastoma) or diffuse (lipoblastomatosis) adipose tumor of childhood, with a morphology that closely resembles the fetal adipose tissue.
- soft and lobulated
- relatively small lesions (2-5 cm), showing fatty looking tissue with gelatinous areas.

Microscopy

- Lipoblastoma shows lobulated architecture with an admixture of mature and immature adipocytes, the latter corresponding to lipoblasts in various stages of development.
- Depending of age of the patient, the lipoblast may be very scarse and lesion may be dominated by lipoma-like component (mostly in older patients).
- Connective tissue septa separate lobules.
- The lobulation is less prominent in lipoblastomatosis.
- The matrix can be quite myxoid, with a plexiform vascular pattern, thus mimicking myxoid liposarcoma.
- Occasionally lipoblastoma(tosis) may show extramedulary hematopoiesis or cells resembling brown fat. Cellular maturation has been described, leading to lipoma-like picture.

Pathological synopsis

- lipoblasts
- very focal lobulation
- myxoid stroma
- +/- atypical stromal nuclei
- Closely resembles fetal fat
- nodules of adipose and myxoid tissue demarcated by bands of fibrous tissue.
- The cells displayed a range of differentiation from multivacuolated lipoblasts to mature adipocytes.
- Mitoses are nonexistent to rare
- Histologic variations :

  • subtle zonal architecture of fat maturation
  • abundant myxoid material
  • primitive mesenchymal cells
  • focal plexiform vascular pattern
  • multinucleated cells.

Immunochemistry

- immunopositivity

  • S100 (100%)
  • CD34 (100%)
  • Mib-1 reactivity : absent to low.

Associations (17%) (#19738456#)

- macrocephaly
- seizures
- developmental delay
- autism
- congenital anomalies
- Sturge-Weber syndrome
- family history of multiple lipomas
- hemangioma (#9331284#)
- lipoma (#9331284#)
- juvenile aponeurotic fibroma (#9331284#)

The degree of adipocytic differentiation does not predict biologic behavior.

Differential diagnosis

- lipoma
- myxoid liposarcoma

  • due to presence of: lipoblasts, plexiform vascular pattern, abundant myxoid stroma
  • Ultrastructurally similar to myxoid liposarcoma
  • lipoblastoma is distinguished from myxoid liposarcoma by: young age of patient, distinct lobulation, absence of giant cells or pleomorphic nuclei

- pleomorphic liposarcoma of soft tissues

Variants

- mature lipoblastoma
- lipoblastomatosis (lipoblastoma with irregular margins)

Localization

- soft tissues (extremities, trunk, head and neck) (#15214818#)
- intrascrotal lipoblastoma (#15214818#)
- pulmonary lipoblastoma

Immunochemistry

In immunohistochemical studies, the neoplastic cells are positive for vimentin and stain negatively for other markers, including cytokeratins, CD34, desmin and NKIC3. These markers can be helpful in distinguishing lipoblastoma from the appendageal tumours and other mesenchymal tumours, such as spindle cell lipoma, angiomyofibroblastoma and lipofibromatosis.

Cytogenetics

- chromosome 8 abnormalities (80%)
- nonspecific numerical abnormalities (10%)
- normal karyotype (10%)

82% lipoblastomas had rearrangement of the 8q11 approximately q13 region. These rearrangements target the PLAG1 gene, which becomes upregulated through promoter swapping.

As 8q11 approximately q13 rearrangements have been reported in only 3% of conventional lipomas and never in myxoid liposarcoma, cytogenetic analysis or FISH for the PLAG1 gene can provide useful differential diagnostic information.

- 8q22 rearrangements (PLAG1 rearrangements)

  • t(8;12)(q22;q13) (8q22 and 12q13) (#15214818#)
  • t(8;18)(q22;q23) (8q22 and 18q23) (#15214818#)

- 8q11.2-8q12-8q13 (#7828158#)

  • t(3;8)(q12;q11.2) (#1521225#)
  • t(8;15)(q12;q25) (8q12 and 15q25)
  • t(7;8)(q31;q13) (7q31 and 8q13) (#9530333#)
  • ins(8;6)(q11.2;q13q27) (#9169035#)

- other rearrangements

  • masked 8q intrachromosomal rearrangement

Molecular biology

- PLAG1 rearrangements at 8q22 (69%) (#11549588#)

  • PLAG1-HAS2 fusion by 8q rearrangement

Differential diagnosis

- liposarcomas

  • myxoid/round cell liposarcoma
  • atypical lipomatous tumor tumor (well-differentiated lipoma-like liposarcoma) (#12242528#)
    • MDM2 gene amplification ? (#12242528#)
    • CDK4 gene amplification ? (#12242528#)

The histopathological findings of a lipoblastoma are characterized by lobular architecture and an admixture of mature adipocytes and lipoblasts in various stages of development. The matrix can be myxoid.

The histopathological differential diagnosis of a liposarcoma includes other tumours with adipocytic differentiation, such as atypical lipomatous tumours/well-differentiated liposarcomas, myxoid liposarcomas, and spindle cell lipomas.

Because of the presence of lipoblasts, a lipoblastoma may have a strong resemblance to well-differentiated liposarcomas. Cases with myxoid changes may be extremely difficult to distinguish from myxoid liposarcomas.

The recent innovation of the term lipofibromatosis also adds to the diagnostic difficulty. The degree of the fibroblastic component is generally greater in lipofibromatosis than in lipoblastoma.

Occasionally, there can be difficulties in distinguishing a lipoblastoma from a conventional lipoma or a myxoid liposarcoma. As 8q11 approximately q13 rearrangements have been reported in only 3% of conventional lipomas and never in myxoid liposarcoma. Cytogenetic analysis or FISH for the PLAG1 gene can provide useful differential diagnostic information.

Management

Because lipoblastomas are usually well encapsulated and have little adjacent tissue, the definitive treatment is complete surgical excision.

However, focal recurrence can be a problem in up to 25% of cases, due to incomplete resection.

Despite their ability for local invasion and rapid growth, the prognosis is excellent.

Prognosis

Lipoblastoma is benign and malignant transformation or metastatsis does not occur. Recurrences are described in 9-22% of cases mainly in lipoblastomatosis.

See also

- Tumors

  • soft tissue tumors
    • adipocytic tumors
      • lipoblastomatosis

References

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